This invention relates to improved methods for treatment of cardiac arrhythmias, and more particularly, to novel compounds useful in the treatment of cardiac arrhythmias.
Cardiac arrhythmia may be defined as a variation from the normal rhythm of the heart beat. Different types of arrhythmias are recognized according to the portion of the heart which is affected and the way in which the beat departs from the norm. Thus, atrial flutter and fabrillation, ventriculator flutter and fibrillation, sinus tachycardia and sinus bradycardia are representative arrhythmias.
Cardiac arrhythmias are usually treated by administering drugs which help to restore the normal heartbeat. Such drugs as quinidine, procainamide, lidocaine, and propranolol have been used with some success in treating cardiac arrhythmias. The drugs hitherto used in the therapy of cardiac arrhythmias each have been found to have significant limitations which have made the treatment less than optimally effective and safe. For example, each of the prior art drugs has frequently been found to be useful against only one type of cardiac arrhythmia. Also prior art drugs have generally had a short duration of activity, and have been found to produce undesirable side effects such as gastro intestinal distress, hypotension, myocardial depression, respiratory depression, and central nervous system (CNS) stimulation or depression.
Certain compounds structurally related to the novel compounds of this invention have been disclosed in the prior art.
1-Phenoxy-3-(2-imino-1,2-dihydropyridyl)-2-propanol is disclosed by D. Banerjee, T. K. Das Gupta, S. Mukerji, and B. N. Mitra, Indian J. Chem., 8, 707-709 (1970). The compound was synthesized as an intermediate in the preparation of 1-phenoxy-3-(2-amino-1-piperidine)-2-propanol, a potential anticancer agent. However, neither compound was found to have anticancer activity. No other utility is disclosed by these authors.
1-Phenoxy-3-(2-imino-3-methyl-1,2-dihydropyridyl)-2-propanol is disclosed in H. J. Roth and R. Rohrbach, Archiv. Pharm., 303, 563-578 (1970). The compound was synthesized in the course of a series of experiments on reactions of substituted pyridines with 1,2-epoxides. No utility is disclosed for the compound.
3-(2-METHYLPHENOXY)-1-(2-IMINO-1,2-DIHYDROPYRIDYL)-2-PROPANOL IS DISCLOSED IN Y. M. Beasley, V. Petrow, and O. Stephenson, J. Pharm. and Pharmacol., 10, 47-59 (1958); K. Okamoto and M. Tetsuo, Yakugaku Zasshi, 82, 769-770 (1962); and Japanese Pat. No. 19, 649 (64), issued Sept. 11, 1964. Beasley, et al., mistakenly identify the compound as 3-(2-methylphenoxy)-1-(2-pyridylamino)-2-propanol. They prepared the compound int the course of a search for new analgesics, but no analgesic properties are attributed to this compound. Okamoto, et al., and the Japanese patent both disclose the correct structure for this compound but neither discloses any utility for it.
Thus the prior art has disclosed these three compounds but has not disclosed any pharmacological utility for them.